SION-719 - (PreciSION CF)

September 14, 2026: Sionna Therapeutics (NASDAQ: SION) said it will advance its cystic fibrosis dual combination SION-451 + SION-2222 into the AscenSION CF Phase 2a proof-of-concept trial, expected to start in Q1 2027, after post hoc review of the Phase 2a PreciSION CF trial of SION-719.

In PreciSION CF (NCT07108153), a randomized crossover study in 15 adults with CF homozygous for F508del receiving Trikafta, SION-719 did not meet the key activity endpoint and will not be advanced as an add-on to standard of care. Across 14 evaluable participants, placebo-adjusted sweat chloride change was -1.0 mmol/L in the primary analysis and -1.1 mmol/L in a prespecified secondary analysis. In a post hoc analysis excluding three participants with exposure patterns consistent with non-adherence, mean placebo-adjusted sweat chloride change was -8.6 mmol/L. The company also reported Trikafta component exposures were about 25-30% lower during SION-719 treatment periods and cited possible CFTR biology interactions with ivacaftor as a confounder.

The planned AscenSION CF Phase 2a study will be open-label, treat adults with F508del homozygous CF for 28 days, and assess sweat chloride, safety, and PK after switching from Trikafta to SION-451 + SION-2222.

Separately, Sionna announced a ~46% workforce reduction, about $6.4 million in restructuring charges, and said these measures extend cash runway into 2H 2029.